chr19-12581107-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020714.3(ZNF490):​c.968G>A​(p.Ser323Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF490
NM_020714.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.06
Variant links:
Genes affected
ZNF490 (HGNC:23705): (zinc finger protein 490) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059787273).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF490NM_020714.3 linkc.968G>A p.Ser323Asn missense_variant Exon 5 of 5 ENST00000311437.11 NP_065765.1 Q9ULM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF490ENST00000311437.11 linkc.968G>A p.Ser323Asn missense_variant Exon 5 of 5 1 NM_020714.3 ENSP00000311521.6 Q9ULM2
ENSG00000269693ENST00000593682.1 linkn.-134G>A upstream_gene_variant 1 ENSP00000473043.1 M0R378
ZNF490ENST00000414906.5 linkn.*890G>A downstream_gene_variant 3 ENSP00000402719.1 F8WDW6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251416
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461870
Hom.:
0
Cov.:
38
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.968G>A (p.S323N) alteration is located in exon 5 (coding exon 5) of the ZNF490 gene. This alteration results from a G to A substitution at nucleotide position 968, causing the serine (S) at amino acid position 323 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
3.7
DANN
Benign
0.65
DEOGEN2
Benign
0.022
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.00019
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.51
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.82
N
REVEL
Benign
0.046
Sift
Benign
0.57
T
Sift4G
Benign
0.53
T
Polyphen
0.40
B
Vest4
0.037
MutPred
0.28
Loss of phosphorylation at S323 (P = 0.0517);
MVP
0.13
MPC
0.27
ClinPred
0.069
T
GERP RS
-1.4
Varity_R
0.058
gMVP
0.012

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770027002; hg19: chr19-12691921; API